This is a proposal to establish a Center of Excellence for Autoimmunity at the University of Pennsylvania School of Medicine. The presence of a strong basic science of immunology on the campus, combined with a long-standing standard of excellence in the management of patients with various autoimmune disorders at the Hospital of the University of Pennsylvania, makes Penn the idea place for this Center. The clinical component of the Center consists of three clinical trials: (1) a Phase I/II trial on the use of antibody to Interleukin-12 for the treatment of multiple sclerosis; 2) a Phase I/II trial on the use of Interleukin 12 in the treatment of inflammatory bowel disease; 3) use of anti-CD20 antibody for the treatment of systemic lupus erythematosus. The basic science component is focused on the elucidation of the basic mechanisms of autoimmunity and immunomodulation related to the clinical trial. Project 3 studies the role of Il-12 in the pathogenesis and therapy of multiple sclerosis and its animal counterpart, experimental autoimmune encephalomyelitis. Project 4 focuses on the mechanisms of anti-B cell therapy in systemic lupus erythematosis and its murine model. The Center has two cores-an immunology core to centralize the immunological tests required in all projects, and an administrative core for administration of the Center and facilitation of interaction between clinicians and basic scientists involved in the different projects.